| Eligibility |
Inclusion Criteria:
- Patients who were pathologically confirmed soft tissue sarcoma (soft tissue sarcomas
other than alveolar/embryonal rhabdomyosarcoma, clear cell sarcoma, extraosseous Ewing
sarcoma, alveolar soft tissue sarcoma, well differentiated liposarcoma, extraosseous
myxoid chondrosarcoma, etc.)
- The patient was diagnosed as progressive and the investigators determined that the
lesion was not suitable for surgical treatment
- The patients had not received systemic therapy (including chemotherapy, targeted
therapy and bioimmunotherapy) for advanced soft tissue sarcoma. More than 6 months
have passed since the end of neoadjuvant/adjuvant therapy (including chemotherapy,
targeted therapy, bioimmunotherapy, etc.), and the cumulative dose of adriamycin used
in the past was =100 mg/m2
- In patients with measurable disease, lesions are defined and monitored by RECIST v1.1
- Aged = 18 years old, < 60 years old
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, amputees
can be 0-2
- Expected survival > 3 months
- Adequate organ and bone marrow function, defined as follows: ? Blood routine (14 days
before screening without blood transfusion, without G-CSF, without drug correction):
neutrophil count (ANC) = 1.5 × 10^9/L; platelet count (PLT) = 100 × 10^9/L; hemoglobin
(Hb) = 100 g/L; ? Blood biochemistry: serum creatinine (Cr) = 1.5 × upper limit of
normal (ULN) or creatinine clearance = 60ml/min; total bilirubin (TBIL) = 1.5 × ULN;
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level = 2.5 × ULN,
The subjects with liver metastasis should be = 5 × ULN; ? Coagulation function:
international normalized ratio (INR) = 1.5, prothrombin time (PT) and activated
partial thromboplastin time (APTT) = 1.5 × ULN; ? Urinalysis: urine protein < 2 +; if
urine protein = 2 +, the 24-hour urine protein quantification must be = 1g; ? thyroid
stimulating hormone (TSH) = ULN and = LLN; if abnormal, T3 and T4 levels should be
investigated, normal T3 and T4 levels can be included
- Cardiac function:1) 12-lead electrocardiogram showed no severe arrhythmias, QTcF = 480
ms; 2) No signs of myocardial ischemia; 3) LVEF =55% by cardiac ultrasound (measured
by the biplane Simpson method); 4) NT-proBNP < age cutoff value; 5) Troponin within
normal values.
- Agree and have signed informed consent, willing and able to comply with scheduled
visits, study treatment, laboratory tests and other test procedures
- Women of childbearing potential should have a negative serum or urine pregnancy test
within 72 hours prior to receiving the first dose of study treatment; and should be
willing to use one acceptable contraception (i.e., oral contraceptives, condoms,
intrauterine devices [IUDs]) throughout the period of taking study treatment and for
at least 3 months after the last dose of study drug(s). For men, surgical
sterilization or consent to appropriate contraception during observation and up to 90
days after the last treatment should be used
Exclusion Criteria:
- known allergy to recombinant humanized anti-PD-1 monoclonal antibody drugs and their
components
- Known allergy to recombinant humanized anti-CTLA-4 monoclonal antibody drug and its
components
- known allergy to any component of the cadonilimab formulation
- Patients with cardiac disease class II or higher as determined by the New York Heart
Association (NYHA) score
- Palliative radiotherapy within 2 weeks prior to the first dose
- Other active malignancy within 5 years prior to enrollment. Except for locally curable
malignancies (manifested as cured) such as basal or cutaneous squamous cell carcinoma,
superficial bladder cancer, endometrial carcinoma in situ, cervical carcinoma in situ,
or breast carcinoma in situ
- Concurrent enrollment in another clinical study, unless it is an observational
(non-interventional) clinical study
- Active autoimmune disease requiring systemic therapy within 2 years prior to the start
of study treatment, or autoimmune disease that, in the judgment of the Investigator,
is likely to recur or for which treatment is planned; except for the following: skin
diseases not requiring systemic therapy (e.g., vitiligo, alopecia areata, psoriasis,
or eczema); hypothyroidism due to autoimmune thyroiditis requiring only a stable dose
of hormone replacement therapy; well-controlled type I diabetes mellitus; childhood
well-controlled type I diabetes mellitus; subjects whose childhood asthma has
completely resolved and does not require any intervention in adulthood; and subjects
who, in the judgment of the investigator, have a disease that will not recur in the
absence of external triggers
- Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic
diarrhea) that is active or requires clinical management
- Subjects will require systemic therapy with corticosteroids (>10 mg/day of prednisone
equivalents) or other immunosuppressive medications within 14 days of administration
of study drug. Inhaled or topical topical steroids and adrenal replacement doses >10
mg/day of prednisone equivalent are allowed in the absence of active autoimmune
disease. Topical, ocular, intra-articular, intranasal and inhaled corticosteroids
(with minimal systemic absorption) are permitted in subjects. Physiologic replacement
doses of systemic corticosteroids are permitted, even if >10 mg/day of prednisone
equivalent. Short-term use of corticosteroids is permitted for prophylaxis (e.g.,
contrast allergy) or for treatment of non-autoimmune diseases (e.g., delayed
hypersensitivity reactions due to contact allergens)
- Known history of positive test for human immunodeficiency virus or known acquired
immunodeficiency syndrome
- History of known allogeneic organ transplantation and allogeneic hematopoietic stem
cell transplantation
- Known presence or history of interstitial lung disease
- Received a live vaccine within 30 days prior to the first dose of cadonilimab or plan
to receive a live vaccine during the study period
- Subjects with necrotic lesions detected on examination within 4 weeks prior to
enrollment that, in the judgment of the investigator, pose a risk of major bleeding
- Serious infection, including but not limited to concomitant complications requiring
hospitalization, sepsis, or severe pneumonia, within 4 weeks prior to first dose
- Known active tuberculosis (TB). Subjects suspected of having active TB will be
examined by chest X-ray, sputum, and exclusion by clinical signs and symptoms
- Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV)
carriers with HBV DNA >1000 IU/mL, and patients with active hepatitis C should be
excluded. Inactive hepatitis B surface antigen (HbsAg) carriers, treated and
stabilized hepatitis B patients (HBV DNA <1000 IU/mL), and cured hepatitis C patients
may be enrolled. For HCV Ab-positive subjects, participation in the study is eligible
only if the HCV RNA test result is negative
- Major surgical procedure within 30 days prior to the first dose of cadonilimab or have
not fully recovered from a prior procedure. Localized surgical procedures (e.g.,
systemic port placement, core needle biopsy, and prostate biopsy) are permitted
provided that the procedure is completed at least 24 hours prior to the time of the
first dose of study treatment medication
- Presence of known meningeal metastases, spinal cord compression, molluscum contagiosum
disease, or active brain metastases. However, enrollment is allowed for subjects who
meet the following requirements and have a measurable lesion outside the CNS: 1)
previously untreated and currently asymptomatic (e.g., no neurologic deficits,
seizures, or other signs and symptoms typical of CNS metastases; glucocorticoid
therapy is not required); 2) asymptomatic after treatment has been imaging stable for
at least 4 weeks prior to the initiation of study treatment (e.g., no new or enlarging
brain metastatic lesion ) and have discontinued systemic glucocorticoid and
anticonvulsant medication for at least 2 weeks
- Subjects with pleural effusions, pericardial effusions, or ascites that, in the
judgment of the Investigator, remain unstably controlled using repeated drainage or
other methods
- Uncontrolled co-morbidities, including symptomatic congestive heart failure (grade 3
or 4 as determined by the New York Heart Association functional classification),
uncontrolled hypertension, unstable angina, poorly controlled cardiac arrhythmias,
acute or evidence of ongoing myocardial ischemia, severe active peptic ulcer disease
or gastritis, or mental illness/social disease that would limit the subject's ability
to comply with the study requirements or interfere with the subject's ability to
provide written mental illness/social condition that would limit the subject's ability
to provide informed consent. Any arterial thromboembolic event, including myocardial
infarction, cerebrovascular accident, or transient ischemic attack, history of deep
vein thrombosis, pulmonary embolism, or any other serious thromboembolism within 6
months prior to enrollment
- Unreversed toxicity from prior antineoplastic therapy, defined as toxicity that has
not returned to NCI CTCAE version 5.0 grade 0 or 1, or to a level specified in the
inclusion/exclusion criteria (except alopecia areata). Subjects who experience
irreversible toxicity that is not expected to worsen with administration of study drug
(e.g., hearing loss) may be included in the study after consultation with the Medical
Ombudsman. Subjects with radiotherapy-induced long-term toxicity that, in the judgment
of the Investigator, is not reversible may be included in the study after consultation
with the Medical Ombudsman
- Females who are pregnant or breastfeeding
- Any condition that, in the opinion of the Investigator, may render treatment with the
study drug risky or will interfere with the evaluation of the study drug or the safety
of the subject or the resolution of the study results
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